Variant 3-9890774-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PM1PM2BP4_StrongBP6_ModerateBS1

The NM_032492.4(JAGN1):c.52C>A(p.Gln18Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000429 in 1,610,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

JAGN1
NM_032492.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

JAGN1 (HGNC:26926): (jagunal homolog 1) The protein encoded by this gene is a transmembrane protein. It functions in the early secretory pathway and is necessary for neutrophil differentiation and survival. Mutations in this gene result in severe congenital neutropenia. [provided by RefSeq, Oct 2014]

JAGN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 10 uncertain in NM_032492.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019383073).

BP6

Variant 3-9890774-C-A is Benign according to our data. Variant chr3-9890774-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1128794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000453 (66/1457948) while in subpopulation AMR AF= 0.0015 (66/44138). AF 95% confidence interval is 0.00121. There are 0 homozygotes in gnomad4_exome. There are 25 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAGN1	NM_032492.4 linkuse as main transcript	c.52C>A	p.Gln18Lys	missense_variant	1/2	ENST00000647897.1
JAGN1	NM_001363890.1 linkuse as main transcript	c.-217C>A		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAGN1	ENST00000647897.1 linkuse as main transcript	c.52C>A	p.Gln18Lys	missense_variant	1/2		NM_032492.4	P1
JAGN1	ENST00000489724.2 linkuse as main transcript	c.52C>A	p.Gln18Lys	missense_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

239010

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

129928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1457948

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000122

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.30

T;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.97

N;.;.

REVEL

Benign

0.13

Sift

Benign

0.53

T;.;.

Sift4G

Benign

1.0

T;.;.

Polyphen

0.0

B;.;B

Vest4

0.21

MVP

0.37

MPC

0.27

ClinPred

0.057

GERP RS

5.0

Varity_R

0.25

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over